Figure 4.

Treatment with mesenchymal stem cells (MSCs) of wild-type or interferon-gamma receptor
knockout (IFN-γR KO) origin does not influence the development of collagen-induced
arthritis in DBA/1 mice. Mice were immunized on day 0 with collagen type II (CII) in complete Freund's adjuvant
and injected intravenously with MSCs on day 16 and day 23. The mean arthritic score
(a) and the cumulative incidence of arthritis (b) in DBA/1 mice treated with phosphate-buffered saline (PBS), wild-type MSCs, or IFN-γR
KO MSCs are shown. Error bars represent standard error of the mean (SEM). (c) On day 46, sera of individual mice were analyzed for total anti-CII IgG. Histograms
represent averages ± SEM. (d) Forty-two days after immunization, five mice in each group were challenged with 10
μg of CII in the right ear and vehicle in the left ear. Delayed-type hypersensitivity
responses were measured as the percentage of swelling (100 × [(thickness of the right
ear -- thickness of the left ear)/thickness of the left ear]) at the indicated times.
Histograms indicate averages ± SEM. (e) On day 19 after immunization with CII in complete Freund's adjuvant, DBA/1 wild-type
mice were injected intravenously with 1 × 106 wild-type MSCs, IFN-γR KO MSCs, or PBS, followed by an administration of 10 μg of
anti-CD3 antibody on day 20. On day 21, in vivo T-cell proliferation was measured by detection of 5-ethynyl-2' -deoxyuridine (EdU)
in the T-cell populations in the spleen and lymph nodes by fluorescence-activated
cell sorting analysis. The percentages of EdU-positive cells in the CD4+ and CD8+ populations in the spleen and lymph nodes are shown. Histograms represent averages
of four mice ± SEM.